The renin-angiotensin system is involved in the homeostatic function to control systemic blood pressure, the volume of body fluid, balance among the electrolytes, etc., associated with the aldosterone system. Relation between the renin-angiotensin system and hypertension has been clarified by the development of the inhibitors of angiotensin II (AII) converting enzyme (ACE) which produce angiotensin II having a strong vasoconstrictive action. Since angiotensin II constricts blood vessel to elevate blood pressure via the angiotensin II receptors on the cellular membranes, angiotensin II antagonists, like the ACE inhibitors, can be used for the therapy of hypertension caused by angiotensin II. It has been reported that a number of angiotensin II analogues such as saralasin, [Sar.sup.1, Ile.sup.8 ] AII and the like possess potent angiotensin II antagonism. It has, however, been reported that, peptide antagonists shows a short term action by parenteral administration and they are ineffective by oral administration [M. A. Ondetti and D. W. Cushman, Annual Reports in Medicinal Chemistry, 13, 82-91 (1978)].
On the other hand, for solving the problems observed in these peptide angiotensin II antagonists, studies on non-peptide angiotensin II antagonists have been developed. In the earliest studies in this field, imidazole derivatives having angiotensin II antagonism have been disclosed in Japanese patent unexamined publication No. 56-71073 (JPA 56-71073), JPA 56-71074, JPA 57-98270 and JPA 58-157768, U.S. Pat. Nos. 4,355,040 and 4,340,598, etc. Later, improved imidazole derivatives are disclosed in EP-0253310, EP-0291969, EP-0324377, EP-403158, WO-9100277, JPA 63-23868 and JPA H-117876; pyrrole, pyrazole and triazole derivatives in EP-0323841, EP-0409332 and JPA 1-287071; benzimidazole derivatives in U.S. Pat. No. 4,880,804, EP-0392317, EP-0399732, EP-0400835 and JPA 3-63264; azaindene derivatives in EP-0399731; pyrimidone derivatives in EP-0407342; pyridine derivatives in EP-0475206 and EP-0499415; and quinazolinone derivatives in EP-0411766; as angiotensin II antagonists.
However, in order to become a practically useful therapeutic agent, angiotensin II antagonists are required to have a strong and long acting angiotensin II antagonistic and hypotensive action by oral administration. As shown in so far known literature references, the preferable structural feature as a strong angiotensin II antagonist is considered to have an acid group, for example, tetrazole group or carboxyl group on the biphenyl side chain, especially tetrazole group as most preferable one and clinical test of compounds having the tetrazole group for anti-hypertension agents is conducted [Y. Christen, B. Waeber, J. Nussberger, R. J. Lee, P. B. M. W. M. Timmermans, and H. R. Brunner, Am. J. Hypertens., 4, 350S (1991)]. However, compounds having tetrazole ring and azide compounds to be used for synthesizing them have been known as involving a danger of explosion, which becomes a serious problem to the large scale preparation and industrial production.
The present inventors considered that compounds acting to control renin-angiotensin system as well as being clinically useful for the treatment of circulatory diseases such as hypertension, cardiopathy (hypercardia, heart failure, cardiac infarction, etc.), cerebral apoplexy, and improving cerebral function, are required to have an angiotensin II receptor antagonistic activity and also have a strong and long active angiotensin II antagonistic activity and hypotensive action by oral administration, and they have made extensive and intensive studies.
As a result, the present inventors have found a novel cyclic compounds having a potent angiotensin II receptor antagonistic activity as well as a long-acting and strong AII antagonistic and anti-hypertensive actions by oral administration. The present inventors have further developed studies to accomplish the present invention.